Peripheral bacterial endotoxin administration triggers both memory consolidation and reconsolidation deficits in mice

Vulnerability to Disease as a Predictor of Faster Life History Strategies

“…Some of the most extensively investigated instances of peripherally produced proinflammatory cytokines influencing brain and behavior include numerous studies that have shown that cytokines (e.g., during bouts of sickness or cytokine-based treatment therapies) trigger depressive behaviors (Gershenfeld et al 2005;KiecoltGlaser et al 2002;Raison et al 2006), that cytokines may induce a constellation of biologically adaptive behaviors known as Bsickness behaviors^that enforce rest, keep infected animals safe from predation, and maximize recovery ( Aubert et al 1995;Dantzer and Kelley 2007;Konsman et al 2002;McLinden et al 2012;Shattuck and Muehlenbein 2015), and that cytokines significantly impact numerous aspects of learning/memory/plasticity, such as acquisition (Sparkman et al 2005), memory consolidation (Barrientos et al 2002;Kranjac et al 2012;Pugh et al 1998), and memory reconsolidation . Therefore, given the strong evidence that peripheral immune activity signals the CNS, and produces distinct changes in neural, neuroendocrine, and behavioral parameters, it is entirely plausible that an individual's physiology is not only subconsciously Baware^of ongoing internal infectious events, but also may construct, throughout the course of life, a general awareness or internal model of her/his own immune competence, a model that may influence life history strategy.…”

Interleukin-1β-induced memory reconsolidation impairment is mediated by a reduction in glutamate release and zif268 expression and α-melanocyte-stimulating hormone prevented these effects

“…It was also reported that peripheral administration of LPS in mice produced deficits in both memory consolidation and reconsolidation (Kranjac et al, 2012). However, LPS-induced effects on memory reconsolidation processes in this experimental model seem to be mediated by a zif-268-independent mechanism.…”

“…The effects of immune activation or cytokines on memory reconsolidation have been studied far less (Machado et al, 2010;Kranjac et al, 2012). We recently shown that IL-1b infused directly into the hippocampus may also have a detrimental effect on reconsolidation of contextual fear memory (Machado et al, 2010).…”

Proteinase-activated receptor 2 is involved in the behavioural changes associated with sickness behaviour

“…In addition, there is evidence that LPS induces elevated levels of other potential endogenous PAR2 activators Kirshenbaum et al, 2008) but whether these contribute to the role of PAR2 in the onset and maintenance of sickness behaviour either by crossing the BBB or by induction of their production within the brain itself requires further investigation. In addition to LPS resulting in sickness-like behaviour, administration of LPS has also been shown to impair cognitive function as evidenced in tests of avoidance learning , contextual fear conditioning Kranjac et al, 2012), novel object recognition (Miwa et al, 2011) and spatial memory tests (Shaw et al, 2001; as well as exacerbating memory deficits in a mouse model of delirium (Field et al, 2012;Griffin et al, 2013). Whilst not the focus of the present study, one could speculate that PAR2 deletion may also impair LPS-induced cognitive deficits and indeed this warrants further investigation.…”